The National Center for Complementary and Alternative Medicine research funding priorities emphasize and encourage studies of mechanisms of action underlying complementary and alternative medicine approaches. Our proposed research examines the mechanism of manipulative and body-based interventions for musculoskeletal pain and includes state-of-the-art techniques for examining pain sensitivity such as quantitative sensory testing and functional magnetic resonance imaging of the brain. LBP is one of the most common forms of chronic musculoskeletal pain. Manipulative and body-based interventions have consistently shown clinical effectiveness in patients with LBP. Although mechanisms are not fully understood, our data, and that of others, indicates that body-based interventions may modulate aspects of the central sensitization of pain. The primary objective for this study is to compare the effect of manipulative and body-based interventions commonly used in the management of LBP on behavioral /psychophysical and cortical measures of pain sensitivity and central sensitization of pain. Use of a model of experimentally induced low back pain that resulted in meaningful and measurable pain allows a unique opportunity to investigate the effects of manipulative and body-based interventions without some of the clinical confounds. The secondary objective of the proposal is to collect longitudinal data to examine both facilitation and inhibition of pain sensitivity. This combination of experimental design with control groups and longitudinal collection of pain- related brain imaging presents a unique opportunity to study the mechanisms facilitation and inhibition of musculoskeletal pain. 180 participants will be randomly assigned to receive one of the interventions or be in a control group. We will collect fMRI and psychophysical data about pain sensitivity before and after the induction of pain, and before and after interventions for that pain. The central hypothesis for this proposal is that SMT, a specific form of manipulative and body-based inhibits central sensitization of pain normalizing pain sensitivity more rapidly than other interventions. The specific aims for this proposal are to 1) test immediate effect of manipulative and body-based interventions and the temporal parameters of these effects, 2) examine central changes during the transition from pain free to painful states and 3) determine whether intervention inhibits or normalizes pain sensitivity. The completion of the proposed study will elucidate underpinning mechanisms of manipulative and body-based interventions. The lack of an identifiable mechanism of action may limit the acceptance of manipulative and body-based interventions by traditional medical providers despite the findings of studies supporting the effectiveness of these interventions. Identification of these mechanisms will improve the clinical application and utilization of these interventions in the management of musculoskeletal pain conditions, especially LBP. PUBLIC HEALTH RELEVANCE: The magnitude of the social and economic burden of chronic LBP has led to its description as a public health epidemic. Manipulative and body-based interventions may inhibit or reduce central sensitization of pain that has been linked to chronic pain conditions. Interventions that modulate central sensitization of pain may decrease the likelihood of developing or maintaining a chronic pain state. Identifying these therapies will improve management of chronic musculoskeletal pain conditions reducing the impact of LBP on healthcare and society.